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Glossing is a widely used and examined vocabulary learning tool, and one of the major branches of glossing research has compared the relative effects of first language (L1) and second language (L2) glosses on reading comprehension and vocabulary learning. However, the findings in this literature have not been consistent, calling for a comprehensive and systematic review. To this end, we conducted a meta-analysis to investigate the relative effects of L1 and L2 glossing on L2 reading comprehension and L2 vocabulary learning. Based on 78 effect sizes gathered from 26 studies representing 30 independent samples (N = 2,189), we found that L1 glossing was more effective than L2 glossing in general (Hedge’s g = .33, SE = .09, p < .001), but the effect size may vary depending on the target outcome measure. The relative effectiveness of L1 glossing was particularly supported by the results of immediate posttests of vocabulary, rather than delayed posttests of vocabulary and reading comprehension tests. Further, among a few selected moderator variables, the results of meta-regression revealed that learners’ L2 proficiency level significantly influenced the average effectiveness, such that L1 glossing is particularly effective for beginner learners compared to those with intermediate or higher L2 proficiency levels.